{"doi":"10.1128/aac.01292-21","title":"Thorough QT Study To Evaluate the Effect of Zoliflodacin, a Novel Therapeutic for Gonorrhea, on Cardiac Repolarization in Healthy Adults","abstract":"Zoliflodacin is a novel spiropyrimidinetrione antibiotic being developed as single oral dose treatment to address the growing global threat of Neisseria gonorrhoeae. To evaluate the cardiac safety of zoliflodacin, a thorough QT/QTc (TQT) study was performed in healthy subjects. In this randomized, double-blind, placebo-controlled, 4-period crossover study, 72 subjects in a fasted state received a single dose of zoliflodacin at 2 g (therapeutic), zoliflodacin at 4 g (supratherapeutic), placebo, and moxifloxacin at 400 mg as a positive comparator. Cardiac repolarization was measured by duration of the corrected QT interval by Fridericia's formula (QTcF). At each time point up to 24 h after zoliflodacin administration, the upper limit of the one-sided 95% confidence interval (CI) for the placebo-corrected change from the predose baseline in QTcF (ΔΔQTcF) was less than 10 ms, indicating an absence of a clinically meaningful increase in QT prolongation. The lower limit of the one-sided multiplicity-adjusted 95% CI of ΔΔQTcF for moxifloxacin was longer than 5 ms at four time points from 1 to 4 h after dosing, demonstrating adequate sensitivity of the QTc measurement. There were no clinically significant effects on heart rate, PR and QRS intervals, electrocardiogram (ECG) morphology, or laboratory values. Treatment-emergent adverse events (AEs) were mild or moderate in severity and transient. This was a negative TQT study according to regulatory guidelines (E14) and confirms that a single oral dose of zoliflodacin is safe and well tolerated. These findings suggest that zoliflodacin is not proarrhythmic and contribute to the favorable assessment of cardiac safety for a single oral dose of zoliflodacin. (This study has been registered at ClinicalTrials.gov under registration no. NCT03613649.).","journal":"Antimicrobial Agents and Chemotherapy","year":2021,"id":196284,"datarank":0.741803878246607,"base_score":2.0794415416798357,"endowment":2.0794415416798357,"self_citation_contribution":0.31191623125197543,"citation_network_contribution":0.42988764699463156,"self_endowment_contribution":0.31191623125197543,"citer_contribution":0.42988764699463156,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":7,"citers_with_citation_signal":7,"citers_with_endowment":7,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9336,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT03613649"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":650934,"name":"Martin Kankam","orcid":"0000-0002-4168-4838","position":1,"is_corresponding":false},{"id":528253,"name":"Aya Nakamura","orcid":"0000-0002-6438-2576","position":2,"is_corresponding":false},{"id":768807,"name":"Tom Conrad","orcid":null,"position":3,"is_corresponding":false},{"id":768808,"name":"John Mueller","orcid":null,"position":4,"is_corresponding":false},{"id":364141,"name":"John O’Donnell","orcid":"0000-0003-0486-778X","position":5,"is_corresponding":false},{"id":768809,"name":"Blaire L. Osborn","orcid":null,"position":6,"is_corresponding":false},{"id":768810,"name":"Kenan Gu","orcid":null,"position":7,"is_corresponding":false},{"id":760390,"name":"George A. Saviolakis","orcid":null,"position":8,"is_corresponding":false},{"id":301170,"name":"Lori M. Newman","orcid":"0000-0001-5464-5208","position":0,"is_corresponding":true}],"reference_count":20,"raw_metadata":null,"created_at":"2026-07-18T23:50:11.609550Z","pmid":"34606332","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}